Different roles for matrix metalloproteinase-2 and matrix metalloproteinase-9 in the pathogenesis of cardiac allograft rejection

Lacey G. Campbell, Sabarinathan Ramachandran, Wei Liu, Michael M. Shipley, Shigeyoshi Itohara, Joseph G. Rogers, Nader Moazami, Robert M. Senior, Andrés Jaramillo

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

Recent studies have shown an increased expression of several matrix metalloproteinases (MMP) during cardiac, renal and pulmonary allograft rejection. To further define the roles of MMP-2 and MMP-9 in the pathogenesis of cardiac allograft rejection, BALB/c cardiac allografts were transplanted into MMP-2-deficient (-/-) and MMP-9-/- mice. Allografts rejected by wild-type mice revealed a significant increase in MMP-2 and MMP-9 expression. MMP-2-deficiency significantly prolonged allograft survival time. Functioning allografts harvested from MMP-2-/- mice showed lower cellular infiltration and fibrosis than rejected allografts harvested from MMP-2+/+ mice at the same time. In contrast, MMP-9-deficiency significantly decreased allograft survival time. Functioning allografts harvested from MMP-9+/+ mice showed lower cellular infiltration and fibrosis than rejected allografts harvested from MMP-9-/- mice at the same time. MMP-2-/- recipients showed decreased T-cell alloreactivity mediated by a defect in dendritic cell stimulatory and T-cell responsive capacities. In contrast, MMP-9-/- recipients showed increased T-cell alloreactivity mediated by a significant increased in dendritic cell stimulatory and T-cell responsive capacities. These results indicate that MMP2 and MMP-9 play significantly different roles in the process of cardiac allograft rejection.

Original languageEnglish (US)
Pages (from-to)517-528
Number of pages12
JournalAmerican Journal of Transplantation
Volume5
Issue number3
DOIs
StatePublished - Mar 2005

Keywords

  • Allograft rejection
  • Dendritic cells
  • Heart
  • Matrix metalloproteinase-2
  • Matrix metalloproteinase-9
  • T-cells

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